In the first 30 months of the study, 891 donors who were deferred from blood donation due to a screening fingerstick hemoglobin of less than 12.5 g/dL ("low hemoglobin" donors) and 406 concurrent "control" donors whose screening fingerstick hemoglobin exceeded 12.5 g/dL were enrolled. The low hemoglobin group contained a greater proportion of female (86 vs 36%) and first time (31 vs 12%) donors compared to the control group. The prevalence of iron deficiency in male donors, defined as a ferritin between 19-29 mcg/L, was 10% in the "low hemoglobin" and 18% in the control men. The prevalence of iron depletion (ferritin less than 19) was 53% in the low hemoglobin and 22% in the control males. In contrast, iron deficiency in female donors (ferritin 9-19 mcg/L) was seen in 31% of both the low hemoglobin and the control groups, whereas iron depletion (ferritin less than 9) was found in 22% and 10% of the low hemoglobin and control women, respectively. Overall, in the low hemoglobin group, 63% of males and 54% of females were either iron depleted or deficient, and in the control group, 40% of both the males and females were iron depleted or deficient. Iron deficiency commonly causes symptoms of fatigue and difficulty concentrating, both of which are difficult to differentiate from high background rates of these complaints. However, several unique symptoms can accompany iron deficiency, including pica, an addictive-like craving to eat non-nutritional substances such as ice, starch, or dirt, and restless legs syndrome. A high incidence of both pica and restless legs syndrome was found in our study, with 8% of all iron deficient or depleted donors exhibiting pagophagia and 12% having restless legs. In contrast, pica was seen in only 3% and restless legs in 9% of the control group. Donors tolerated the once daily dose of ferrous sulfate very well, with 18% having symptoms of mild gastrointestinal upset which resolved upon changing the oral tablet to ferrous gluconate. Only 3% of donors were unable to tolerate any oral formulation of iron due to severe acute gastric discomfort. Sixty days of oral once-daily ferrous sulfate or gluconate resulted in signficant increases in mean hemoglobin, MCV, ferritin, and transferrin saturation, and decreases in mean RDW, despite continued blood donation at a mean of 94 days between successive donations. Verbal screening and laboratory monitoring detected three cases of gastrointestinal blood loss, two cases of B12 deficiency, six cases of uterine bleeding, one case of essential thrombocythemia, seven cases of diabetes, one case of thyrotoxicosis, and 26 cases of thalassemia trait. No GI malignances were found, and no subjects had genetic hemochromatosis. Donors expressed gratitude and satisfaction at the improvement in symptoms and laboratory values produced by oral iron replacement. The effect of iron replacement on the incidence of donor deferral for low fingerstick hemoglobin levels remains under investigation. [unreadable] [unreadable] Iron replacement therapy is a cheap, safe, and effective method of preventing iron deficiency in blood donors, and has added advantages of decreasing donor deferrals and enhancing donor well-being, thereby increasing overall donor satisafaction and retention. A cost-benefit analysis and analysis of the effect of iron intervention on successful donation outcomes as a percentage of donor visits will be performed when the study is completed.